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C Phelps

Publications and source records attributed to C Phelps.

At least 19 recordsLinked to original sources
PubMed2005

13C-carrier DNA shortens the incubation time needed to detect benzoate-utilizing denitrifying bacteria by stable-isotope probing.

The active bacterial community able to utilize benzoate under denitrifying conditions was elucidated in two coastal sediments using stable-isotope probing (SIP) and nosZ gene amplification. The SIP method employed samples from Norfolk Harbor, Virginia, and a Long-Term Ecosystem Observatory (no. 15) off the coast of Tuckerton, New Jersey. The SIP method was modified by use of archaeal carrier DNA in the density gradient separation. The carrier DNA significantly reduced the incubation time necessary to detect the (13)C-labeled bacterial DNA from weeks to hours in the coastal enrichments. No denitrifier DNA was found to contaminate the archaeal (13)C-carrier when [(12)C]benzoate was used as a substrate in the sediment enrichments. Shifts in the activity of the benzoate-utilizing denitrifying population could be detected throughout a 21-day incubation. These results suggest that temporal analysis using SIP can be used to illustrate the initial biodegrader(s) in a bacterial population and to document the cross-feeding microbial community.

Bacteria↗
PubMed2004

Delivering information about cancer genetics via letter to patients at low and moderate risk of familial cancer: a pilot study in Wales.

Increasing demands upon specialist cancer genetics services have resulted in a need to explore alternative means of delivering genetic risk information to individuals at low-risk of familial cancer. This pilot study investigates patient satisfaction with a letter to low and moderate risk individuals notifying them of their risk. Sixty-six people completed a questionnaire designed to measure satisfaction with the way they had been notified of their cancer risk. Two key findings emerge from the data: first of all, whilst many respondents indicated overall satisfaction with the risk letter, a substantial number wanted more information about their risk; and secondly, low-risk individuals in this study are less reassured by and less satisfied with the risk letter than those at moderate risk. The optimal service provision for delivery of genetic risk information is likely to be one which can best respond to individual differences in information-seeking, distress and risk comprehension. There is a need therefore, for a randomised control trial to compare the effectiveness of a risk notification letter with more traditional telephone risk counselling and the implications of each mode of delivery upon the resources of specialist cancer genetics services.

Adult↗
PubMed2001

CEPU-1 expression in the early embryonic chick brain.

We describe the expression pattern of CEPU-1, a cell adhesion molecule of the immunoglobulin superfamily, in the early chick embryo brain. An initially broad domain of expression, encompassing forebrain, midbrain and anterior hindbrain, is subsequently narrowed down to a ring-shaped domain at the midbrain-hindbrain boundary, co-localizing precisely with the expression of Wnt1 at the isthmus. In addition, CEPU-1 is expressed in the dorsal aspect of rhombomere 4 and its emigrating neural crest cells. Later in development, we also find CEPU-1 expression in other parts of the developing nervous system such as sensory ganglia and in the ventral aspect of forebrain, midbrain and hindbrain.

Animals↗
PubMed2001

Preimplantation screening for transgenesis using an embryonic specific promoter and green fluorescent protein.

We report enrichment in the efficiency of generating mice transgenic for expression of a human protein in their milk using GFP-mediated preimplantation screening. The transgene array consisted of a functional gene (human alpha-1 antitrypsin under the control of the ovine BLG promoter) linked 5' to a reporter gene (GFP under the control of the murine Oct-4 promoter). GFP expression was detected in blastocysts by fluorescence microscopy and green and nongreen embryos were transferred to recipients in separate groups. In the first experiment, of seven pups that resulted from the transfer of blastocysts expressing GFP, five (71%) were transgenic. The experiment was repeated and of 12 pups that resulted from transfer of GFP-expressing blastocysts, 11 were transgenic (92%). The presence of the reporter cassette used for preimplantation screening did not affect the expression level of alpha-1-antitrypsin in the milk of the transgenic mice. In addition, in a related experiment wherein the GFP reporter gene was co-injected with a second mammary-specific transgene, pINC, no effect on transgene expression was observed. For mice transgenic for the mammary-specific gene alone, expression levels for four different lines were 192, 197, 382, and 415 microg/mL. For mice transgenic for both the mammary-specific transgene and the Oct4-GFP reporter cassette, expression levels for seven different lines were 282, 321, 468, 497, 499, 516, and 806 microg/mL.

Animals↗
PubMed2001

Anaerobic mineralization of stable-isotope-labeled 2-methylnaphthalene.

An active sulfate-reducing consortium that degrades 2-methylnaphthalene (2-MNAP) at rates of up to 25 microM x day(-1) was established. Degradation was inhibited in the presence of molybdate and ceased in the absence of sulfate. As much as 87% of 2-[14C]MNAP was mineralized to 14CO2. 2-Naphthoic acid (2-NA) was detected as a metabolite, and incubation with either deuterated 2-MNAP or [13C]bicarbonate indicates that 2-NA is the result of oxidation of the methyl group. Also detected were carboxylated 2-MNAPs, suggesting the presence of an alternative pathway for 2-MNAP degradation.

Anaerobiosis↗
PubMed2000

Differential binding of cAMP-dependent protein kinase regulatory subunit isoforms Ialpha and IIbeta to the catalytic subunit.

Limited trypsin digestion of type I cAMP-dependent protein kinase holoenzyme results in a proteolytic-resistant Delta(1-72) regulatory subunit core, indicating that interaction between the regulatory and catalytic subunits extends beyond the autoinhibitory site in the R subunit at the NH(2) terminus. Sequence alignment of the two R subunit isoforms, RI and RII, reveals a significantly sequence diversity at this specific region. To determine whether this sequence diversity is functionally important for interaction with the catalytic subunit, specific mutations, R133A and D328A, are introduced into sites adjacent to the active site cleft in the catalytic subunit. While replacing Arg(133) with Ala decreases binding affinity for RII, interaction between the catalytic subunit and RI is not affected. In contrast, mutant C(D328A) showed a decrease in affinity for binding RI while maintaining similar affinities for RII as compared with the wild-type catalytic subunit. These results suggest that sequence immediately NH(2)-terminal to the consensus inhibition site in RI and RII interacts with different sites at the proximal region of the active site cleft in the catalytic subunit. These isoform-specific differences would dictate a significantly different domain organization in the type I and type II holoenzymes.

Amino Acid Sequence↗
PubMed1999

Construction, expression, purification and functional analysis of recombinant NFkappaB p50/p65 heterodimer.

NFkappaB plays an important role in mediating the gene expression of numerous cellular processes such as growth, development, the inflammatory response and virus proliferation. The p50/p65 heterodimer is the most abundant form of the NFkappaB dimers and plays a more elaborate role in gene regulation. Biochemical research on p50/p65 NFkappaB has not benefited however from the availability of easily purified recombinant protein. We report two methods for the large scale expression and purification of recombinant NFkappaB p50/p65 heterodimer. The first utilizes a bacterial double expression vector which contains two ribosomal binding sites to facilitate the coexpression of the polypeptides in the p50/p65 NFkappaB heterodimer. The second method uses a mixed protein refolding strategy. Both methods yield crystallizable protein. Electrophoretic mobility shift assays confirm that the DNA binding affinity is independent of the method used to purify the protein. These methods will facilitate the numerous studies on various NFkappaB/Rel family members.

Binding Sites↗
PubMed1999

Transgenic mice overexpressing the growth-hormone-releasing hormone gene have high concentrations of tachykinins in the anterior pituitary gland.

According to recent reports, substance P (SP) is localized in the anterior pituitary gland within subsets of thyrotropes and somatotropes, although earlier electron-microscopic studies described the presence of this tachykinin in mammotropes and gonadotropes. Transgenic mice overexpressing the growth-hormone-releasing hormone (GHRH) gene have markedly enlarged pituitary glands, due to hyperstimulation of the somatotropes. Therefore, we speculated that if somatotropes are able to synthesize tachykinins, these peptides should be greatly increased in the anterior pituitary of transgenic GHRH mice. We found that, in accordance with our working hypothesis, both SP and neurokinin A (NKA) were markedly increased in the anterior pituitary gland of male and female transgenic mice, compared with their respective normal controls. In male transgenic mice, NKA was 13.6- and SP 20.2-fold higher than in the anterior pituitary from normal mice. In female transgenic mice, NKA was 40- and SP 100-fold higher than in the anterior pituitary from normal female mice. In male transgenic mice, NKA and neuropeptide K (NPK) contents in the anterior pituitary showed no significant changes between 26 and 50 days of age but significantly increased between 50 days and 5 months of age. The concentration of NKA in the anterior pituitary did not show significant differences between 26 days and 5 months of age, but NPK concentrations in the anterior pituitary significantly decreased with age. In female transgenic mice, NKA content and concentration in the anterior pituitary increased after 35 days of age, but NPK concentrations significantly decreased after 26 days of age. Triiodothyronine markedly decreased anterior pituitary tachykinins, but ovariectomy and estrogen administration failed to significantly affect tachykinin concentrations in the anterior pituitary of transgenic mice. Tachykinin immunostaining was detected in some somatotropes, but tachykinins were also present in cells that were not GH positive. These findings indicate that hyperstimulated somatotropes contain increased stores of tachykinins and that these cells are a source of tachykinins in the anterior pituitary. Tachykinin stores in the anterior pituitary of transgenic mice were affected by thyroid hormones but seem to be insensitive to estrogens. The GHRH transgenic mice may be an interesting model to study the regulation of tachykinin stores in the anterior pituitary gland.

Animals↗
PubMed1998

The fatty acid composition of maternal diet affects the response to excitotoxic neural injury in neonatal rat pups.

Fatty acids and their derivatives play a role in the response to neural injury. The effects of prenatal and postnatal dietary fatty acid composition on excitotoxic neural injury were investigated in neonatal rat pups. Dams were fed during gestation and lactation a diet whose fat source was either corn oil or menhaden fish oil. On postnatal day 3, litters were culled to 10 per dam. On postnatal day 4, excitotoxic neural injury was induced by infusion of the glutamate analog N-methyl-DL-aspartate (NMA) into the left cerebral hemisphere. Three days later, pups were killed and brains were removed for histological and volume assessments. Levels of arachidonic acid were 2.3-fold higher in cerebrums of pups in the corn oil group than in the fish oil group. Left cerebral hemispheres among all pups were atrophic. Right cerebral hemispheres of pups in the corn oil group showed more histological evidence of edema, and had significantly higher volumes than pups in the fish oil group (66 vs. 42 mm2, p=0.007). These data suggest that the fatty acid composition of prenatal and/or postnatal diet can affect the neonatal response to excitotoxic neural injury.

Animals↗
PubMed1998

Interferon-containing controlled-release polymers for localized cerebral immunotherapy.

Controlled-release ethylene-vinyl acetate copolymers (EVAc), which were used previously for the in vivo intracerebral delivery of chemotherapeutics, were evaluated as a possible route of localized intracerebral delivery of interferon (IFN). Natural mouse IFN-alpha/beta (Mu-IFN-alpha/beta) was incorporated into polymers at 5% or 10% by weight with 2 x 10(4) U or 4 x 10(4) U, respectively. In vitro and in vivo studies of the release of Mu-IFN-alpha/beta from EVAc polymers showed the released IFN to be biologically active, as determined by the inhibition assay of viral cytopathic effect (CPE). Evaluation of the in vitro kinetics of release showed that most of the IFN activity was released in the first 4 days, with the rest being released thereafter. The in vivo kinetic release of Mu-IFN-alpha/beta from intracerebrally implanted polymers showed that most of the IFN activity was released within 24 h after polymer implantation in the hemisphere ipsilateral to the polymer. This IFN activity gradually decreased over the next 72 h, with a significant linear trend (p < 0.0001). The hemisphere contralateral to the implanted polymer showed no significant levels of IFN activity throughout the 4 days of evaluation. By contrast, blood levels of IFN increased from day 1 to day 4, showing a significant linear trend (p = 0.0125), with IFN levels on day 4 being significantly higher (p < 0.05) than on day 1 after polymer implant. This study demonstrates the feasibility of intracranial controlled local delivery of IFN using a polymer delivery device.

Animals↗
PubMed1996

The effect of interferon-alpha on the pituitary-adrenal axis.

This report concerns the use of a minimum stress animal model for evaluating the neuromodulatory effects of interferon-alpha (IFN-alpha). Male Sprague-Dawley rats, 350-450 g, received jugular catheters and were habituated to handling and sampling arenas. These procedures will minimize stress usually associated with i.v. injections and blood sampling. Natural rat IFN-alpha/beta (RaIFN-alpha/beta) endotoxin free (Lee Biomolecular Research Laboratories, San Diego, CA) or recombinant human IFN-alpha, (rHuIFN-alpha) (a gift from Hoffman La Roche, Nutley, NJ) was injected into rats via catheter at various IFN concentrations. Controls were injected with either (1) vehicle (saline), (2) human or bovine serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Experiments were begun (0 h) at about 0900 h, and blood samples were withdrawn at intervals up to 2 h after IFN or control injections and replaced by the same volume of saline. The concentrations of corticosterone and ACTH in peripheral plasma were measured by radioimmunoassay. Both IFN, when injected at concentrations of 300 or 600 U/g body weight (U/gbw), stimulated an increase above 0 h levels of both hormones in the same animals. Additionally, the stimulation was also evident when compared with plasma hormone levels in animals injected with control substance in a parallel time course. After administration of 150 U/gbw of either IFN, only the increase in the blood corticosterone was significant. These studies demonstrate that both homospecific (RaIFN-alpha/beta) and heterospecific (rHuIFN-alpha) IFN preparations are capable of stimulating the pituitary-adrenal axis.

Adrenal Cortex↗
PubMed1995

Nurse practitioners in a teaching hospital.

The development of a model of care using acute care nurse practitioners in a teaching hospital and the integration of the nurse practitioner into an alternative model of care delivery are discussed. Issues in implementation include lack of understanding about the nurse practitioner role on the part of other members of the health care team, legislative constraints, and the administrative restrictions of teaching hospitals. Education of nurses and physicians regarding the scope of practice of the nurse practitioner role, departmental policy changes, and the development of protocols facilitate the efficiency and utilization of the nurse practitioner in this setting. Specific concerns surrounding costs of a nurse practitioner service and practice differences between the clinical nurse specialist and the acute care nurse practitioner are addressed. Nurse practitioner models of care delivery, which address quality, cost-effective care are on the forefront of tomorrow's health care.

Cost-Benefit Analysis↗
PubMed1993

Effect of prenatal and infancy nurse home visitation on government spending.

A completed series of reports on a randomized trial (N = 400) indicated that, in contrast to comparison services, prenatal and infancy nurse home visitation improved a wide range of maternal and child health outcomes among poor, unmarried, and teenaged women bearing first children in a semirural county in upstate New York. Eighty-nine percent of the sample was white, and all analyses focused on this group. In this article, an analysis of the net cost of the home-visitation program from the perspective of government spending is presented. The average per-family cost of the program in 1980 dollars was $3,246 for the sample as a whole, and $3,133 for low-income families. Treatment differences in government expenditures for Aid to Families with Dependent Children, Food Stamps, Medicaid, and Child Protective Services, minus tax revenues due to maternal employment (also expressed in 1980 dollars), were conceived as government savings. By the time the children were 4 years of age, government savings were $1,772 (95% confidence interval [CI]: -$557, $4,102) for the sample as a whole, and $3,498 (95% CI: $569, $6,427) for low-income families. Within 2 years after the program ended, after discounting, the net cost of the program (program costs minus savings) for the sample as a whole was $1,582 per family. For low-income families, the cost of the program was recovered with a dividend of $180 per family.

Adolescent↗
PubMed1992

Management of behavior disturbance in Alzheimer disease: current knowledge and future directions.

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition.

Activities of Daily Living↗
PubMed1992

Reassessment of preoperative laboratory testing has changed the test-ordering patterns of physicians.

To test the hypothesis that physicians have substantially reduced the ordering of unwarranted preoperative tests, the authors reviewed 2,093 medical records of patients having four surgical procedures performed at three institutions in three cities in 1979, 1981, 1983, 1985 or 1987. Excluding hemoglobin measurements, the incidence of ordering preoperative laboratory tests unwarranted by findings on history or physical examination decreased from 32.2 to 25.9 percent during this decade, representing a 19.6 percent reduction. This decrease was irregular and varied from operation to operation, test to test and institution to institution. Overall, the percentage of preoperative tests ordered that were unwarranted decreased from 66.9 percent in 1979 to 60.1 percent in 1987. Extrapolating these results, the authors estimate that more than $320 million was saved annually by elimination of unwarranted tests and that the potential savings could exceed $1.35 billion a year. Unexpectedly, the preoperative ordering of medically indicated tests also decreased (from 92.9 to 80.9 percent, representing a 12.9 percent reduction). Because the benefit of performing justified tests is probably greater than the benefit of avoiding unwarranted tests, the net change has probably not been beneficial. A better system for obtaining justified tests and for eliminating the unwarranted tests may be necessary before a net benefit occurs. Punitive measures to reduce testing without prior establishment of such a system may save money, but impair health.

Chicago↗
PubMed1990

Clinical drug trials in Alzheimer disease. What are some of the issues?

Clinical drug trials in Alzheimer disease are underway in many locations throughout the world. That experience has uncovered a number of unique difficulties. In response, members of the Alzheimer's Association Medical and Scientific Advisory Board organized meetings with experts from the government, academia, private practice and the pharmaceutical industry. The issues are presented here along with some suggestions to facilitate planning and to avoid problems in future drug trials.

Age Factors↗